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Details

Stereochemistry ACHIRAL
Molecular Formula C17H21NO.2C9H10N4O4
Molecular Weight 731.7549
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BIETANAUTINE

SMILES

CN1C2=C(N(CC(O)=O)C=N2)C(=O)N(C)C1=O.CN3C4=C(N(CC(O)=O)C=N4)C(=O)N(C)C3=O.CN(C)CCOC(C5=CC=CC=C5)C6=CC=CC=C6

InChI

InChIKey=COTYIKUDNNMSDT-UHFFFAOYSA-N
InChI=1S/C17H21NO.2C9H10N4O4/c1-18(2)13-14-19-17(15-9-5-3-6-10-15)16-11-7-4-8-12-16;2*1-11-7-6(8(16)12(2)9(11)17)13(4-10-7)3-5(14)15/h3-12,17H,13-14H2,1-2H3;2*4H,3H2,1-2H3,(H,14,15)

HIDE SMILES / InChI
Molecular Formula C9H10N4O4
Molecular Weight 238.2001
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula C17H21NO
Molecular Weight 255.3547
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Diphenhydramine is an antihistamine which is used in the combination with naproxen sodium for the relief of occasional sleeplessness when associated with minor aches and pains. Diphenhydramine has a role nighttime sleep-aid and naproxen sodium is a pain reliever. In addition, diphenhydramine used in relieving symptoms in patients with moderate-to-severe seasonal allergic rhinitis. Diphenhydramine acts as an antagonist of histamine H1 receptor. Besides, was shown potential to repurpose diphenhydramine as an anti-melanoma therapeutic agent, it induces melanoma cell apoptosis by suppressing STAT3/MCL-1 survival signaling pathway.

CNS Activity

Originator

Rieveschl, G.
13
Curator's Comment: Diphenhydramine was discovered by George Rieveschl, in 1943 at the University of Cincinnati

Approval Year

1946
64
Targets

Targets

Primary TargetPharmacologyConditionPotency
Histamine H1 receptor
315
Target ID: P35367
Gene ID: 3269.0
Gene Symbol: HRH1
Target Organism: Homo sapiens (Human)
Antagonist
2778
Antagonist
2778
 7.9 null [pKi]
Antagonist
2778
Blocker
537
 2.7 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Approved
8429
ALEVE PM

Approved Use

for relief of occasional sleeplessness when associated with minor aches and pains; helps you fall asleep and stay asleep

Launch Date

2014
Palliative
Approved
8429
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
93 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/28967696
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIPHENHYDRAMINE plasma
Homo sapiens
population: UNKNOWN
age: ADOLESCENT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
667 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/3760245
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIPHENHYDRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
887 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/3760245
50 mg single, intravenous
dose: 50 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DIPHENHYDRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
9.2 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/3760245
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIPHENHYDRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
8.5 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/3760245
50 mg single, intravenous
dose: 50 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DIPHENHYDRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
18.3%
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/2369804
DIPHENHYDRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
600 mg single, oral
Overdose
Dose: 600 mg
Route: oral
Route: single
Dose: 600 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22158278/
unknown, 13 months
n = 1
Health Status: unknown
Age Group: 13 months
Sex: F
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/22158278/
Other AEs: QT interval prolonged...
Other AEs:
QT interval prolonged (1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/22158278/
400 mg 1 times / day multiple, oral
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28246565
unhealthy, 28 years
n = 1
Health Status: unhealthy
Condition: insomnia
Age Group: 28 years
Sex: M
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/28246565
Disc. AE: Liver injury, Vomiting...
AEs leading to
discontinuation/dose reduction:
Liver injury (1 patient)
Vomiting (1 patient)
Jaundice (1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/28246565
50 mg single, intravenous
Dose: 50 mg
Route: intravenous
Route: single
Dose: 50 mg
Sources:
https://clinicaltrials.gov/ct2/show/NCT01967433
unhealthy
n = 61
Health Status: unhealthy
Condition: Opioid dependence
Population Size: 61
Sources:
https://clinicaltrials.gov/ct2/show/NCT01967433
Other AEs: Hypertension...
Other AEs:
Hypertension (below serious, 5 patients)
Sources:
https://clinicaltrials.gov/ct2/show/NCT01967433
AEs

AEs

AESignificanceDosePopulation
QT interval prolonged 1 patient
600 mg single, oral
Overdose
Dose: 600 mg
Route: oral
Route: single
Dose: 600 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22158278/
unknown, 13 months
n = 1
Health Status: unknown
Age Group: 13 months
Sex: F
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/22158278/
Jaundice 1 patient
Disc. AE
400 mg 1 times / day multiple, oral
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28246565
unhealthy, 28 years
n = 1
Health Status: unhealthy
Condition: insomnia
Age Group: 28 years
Sex: M
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/28246565
Liver injury 1 patient
Disc. AE
400 mg 1 times / day multiple, oral
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28246565
unhealthy, 28 years
n = 1
Health Status: unhealthy
Condition: insomnia
Age Group: 28 years
Sex: M
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/28246565
Vomiting 1 patient
Disc. AE
400 mg 1 times / day multiple, oral
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28246565
unhealthy, 28 years
n = 1
Health Status: unhealthy
Condition: insomnia
Age Group: 28 years
Sex: M
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/28246565
Hypertension below serious, 5 patients
50 mg single, intravenous
Dose: 50 mg
Route: intravenous
Route: single
Dose: 50 mg
Sources:
https://clinicaltrials.gov/ct2/show/NCT01967433
unhealthy
n = 61
Health Status: unhealthy
Condition: Opioid dependence
Population Size: 61
Sources:
https://clinicaltrials.gov/ct2/show/NCT01967433
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737
substrate
1037
substrate
1217

inhibitor
1852

OverviewOther

Other InhibitorOther SubstrateOther Inducer
OCT1
512

OCT2
647

OCT3
150

MATE1
306

MATE2
263
CYP1A1
349

CYP1A2
1054

CYP2A6
543

CYP2B6
664

CYP2C8
693

CYP2C18
138

CYP2C19
991

CYP2E1
667

CYP3A5
395

CYP4A11
119

UGT1A3
422

UGT1A4
347

UGT2B10
127
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2D6
1891
 weak [IC50 11 uM]
yes (co-administration study)
Comment: diphenhydramine coadministration significantly altered the pharmacokinetics, heart rate, systolic blood pressure, and peak acceleration response of metoprolol in extensive metabolizers but not in poor metabolizers
OCT2
648
 yes [IC50 15 uM]
OCT1
543
 yes [IC50 3.4 uM]
OCT3
150
 yes [IC50 695 uM]
MATE2
263
 yes [Ki 266.5 uM]
MATE1
308
 yes [Ki 87 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP2D6
1217
 major
UGT2B10
127
 major
CYP1A2
1054
 minor
CYP2C19
991
 minor
UGT1A3
422
 minor
UGT1A4
347
 minor
CYP2A6
543
 no
CYP2E1
667
 no
CYP4A11
119
 no
CYP1A1
349
 weak
CYP2B6
664
 weak
CYP2C18
138
 weak
CYP2C8
693
 weak
CYP2C9
1037
 weak
CYP3A4
1737
 weak
CYP3A5
395
 weak
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:4636
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4636
ChemicalBook
CB6196202
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6196202
MolPort
MolPort-001-783-508
https://www.molport.com/shop/molecule-link/MolPort-001-783-508
ZINC
ZINC000000020244
http://zinc15.docking.org/substances/ZINC000000020244
eMolecules
716786
https://www.emolecules.com/cgi-bin/more?vid=716786
PubMed

PubMed

TitleDatePubMed
Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines).
1985 Nov-Dec
Diphenhydramine.
1986 Feb
Diphenhydramine: pharmacokinetics and pharmacodynamics in elderly adults, young adults, and children.
1990 Jul
A patient with anaphylaxis to diphenhydramine without cross-reactivity to loratadine.
2018 May-Jun
Patents

Patents

US9592197
10

Sample Use Guides

In Vivo Use Guide
occasional sleeplessness: do not take more than directed; drink a full glass of water with each dose, adults and children 12 years and over: take 2 caplets at bedtime, do not take more than 2 caplets in 24 hours, if taken with food, this product may take longer to work
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: In vitro, [14C] diphenhydramine was accumulated by a saturable, energy-requiring system in choroid plexus. The results show that diphenhydramine, unlike diazepam, is transported between blood, brain and cerebrospinal fluid, in part, by saturable, carrier-mediated transport processes at both the blood-brain and blood-cerebrospinal fluid barriers.
Unknown
Substance Class Chemical
Created
by admin
on Fri Dec 15 18:07:42 GMT 2023
Edited
by admin
on Fri Dec 15 18:07:42 GMT 2023
Record UNII
F3D8G86A29
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BIETANAUTINE
Common Name English
DIPHENHYDRAMINE DI(ACEFYLLINATE) [MI]
Common Name English
1,2,3,6-TETRAHYDRO-1,3-DIMETHYL-2,6-DIOXO-7H-PURINE-7-ACETIC ACID COMPD WITH 2-(DIPHENYLMETHOXY)-N,N-DIMETHYLETHANAMINE (2:1)
Common Name English
DIPHENHYDRAMINE ACEFYLLINATE
WHO-DD  
Common Name English
O-BENZHYDRYLDIMETHYLAMINOETHANOL BIS(THEOPHYLLINE 7-ACETATE)
Common Name English
Diphenhydramine acefyllinate [WHO-DD]
Common Name English
NAUTAMINE
Brand Name English
DIPHENHYDRAMINE DI(ACEFYLLINATE) [MART.]
Common Name English
DIPHENHYDRAMINE DI(ACEFYLLINATE)
MART.   MI  
Common Name English
DIPHENHYDRAMINE DIACEFYLLINATE
Common Name English
Classification Tree Code System Code
WHO-ATC N04AB01
Created by admin on Fri Dec 15 18:07:43 GMT 2023 , Edited by admin on Fri Dec 15 18:07:43 GMT 2023
Code System Code Type Description
CAS
6888-11-5
Created by admin on Fri Dec 15 18:07:43 GMT 2023 , Edited by admin on Fri Dec 15 18:07:43 GMT 2023
PRIMARY
FDA UNII
F3D8G86A29
Created by admin on Fri Dec 15 18:07:43 GMT 2023 , Edited by admin on Fri Dec 15 18:07:43 GMT 2023
PRIMARY
SMS_ID
100000090136
Created by admin on Fri Dec 15 18:07:43 GMT 2023 , Edited by admin on Fri Dec 15 18:07:43 GMT 2023
PRIMARY
MERCK INDEX
m4609
Created by admin on Fri Dec 15 18:07:43 GMT 2023 , Edited by admin on Fri Dec 15 18:07:43 GMT 2023
PRIMARY Merck Index
EVMPD
SUB01767MIG
Created by admin on Fri Dec 15 18:07:43 GMT 2023 , Edited by admin on Fri Dec 15 18:07:43 GMT 2023
PRIMARY
PUBCHEM
11607326
Created by admin on Fri Dec 15 18:07:43 GMT 2023 , Edited by admin on Fri Dec 15 18:07:43 GMT 2023
PRIMARY
RXCUI
236260
Created by admin on Fri Dec 15 18:07:43 GMT 2023 , Edited by admin on Fri Dec 15 18:07:43 GMT 2023
PRIMARY RxNorm
Related Record Type Details
Structure of DIPHENHYDRAMINE
PARENT -> SALT/SOLVATE
Structure of ACEFYLLINE
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of DIPHENHYDRAMINE
ACTIVE MOIETY
Structure of ACEFYLLINE
ACTIVE MOIETY
NIH
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